Serum
high-density lipoprotein-cholesterol (HDL-C) is a risk factor considered to be protective of
atherosclerosis. However,
atherosclerosis is an inflammatory disease and contributes to impairment in
high-density lipoprotein (HDL) function, including reductions in HDL-C, HDL
antioxidant and anti-inflammatory activities.
Anthocyanins are
polyphenols that have demonstrated
antioxidant and anti-inflammatory properties. The objective of this study was to determine whether an
anthocyanin-rich
black elderberry extract (Sambucus nigra) (BEE) (13%
anthocyanins) would protect against
inflammation-related impairments in HDL function and
atherosclerosis in
apoE(-/-) mice, a mouse model of
hyperlipidemia and HDL dysfunction. We fed an AIN-93M diet supplemented with 1.25% (w/w) BEE or control diet to 10 week old male
apoE(-/-) mice for 6 weeks. The BEE fed to mice was rich in
cyanidin 3-sambubioside (∼ 9.8% w/w) and
cyanidin 3-glucoside (∼ 3.8% w/w). After 6 weeks, serum
lipids did not differ significantly between groups, while
aspartate transaminase (AST) and fasting
glucose were reduced in BEE-fed mice. Hepatic and intestinal
mRNA changes with BEE-feeding were consistent with an improvement in HDL function (Apoa1, Pon1, Saa1, Lcat, Clu) and a reduction in hepatic
cholesterol levels (increased Ldlr and Hmgcr, reduced Cyp7a1). In BEE-fed mice, serum
paraoxonase-1 (PON1)
arylesterase activity was significantly higher. In addition, mice fed BEE had significantly lower serum
chemokine (C-C motif) ligand 2 (CCL2) compared to control-fed mice. Notably, we observed significant reductions in total
cholesterol content of the aorta of BEE-fed mice, indicating less
atherosclerosis progression. This study suggests that black elderberry may have the potential to influence HDL dysfunction associated with chronic
inflammation by impacting hepatic gene expression.